A Phase 1/2 interventional study of Ticagrelor in Critical Limb Ischemia, sponsored by University of Southern California. Completed at 1 site in United States. Open to participants aged 18 Years to 80 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-06-19.
Sponsored by University of Southern California · Phase 1/2, Interventional, and Screening
Critical Limb Ischemia (CLI) is defined as limb pain that occurs at rest, or impending limb loss that is caused by severe compromise of blood flow to the affected extremity. CLI is a major cause of death and disability (secondary to myocardial infarction, stroke and amputation). The mortality in patients with CLI approaches 13-25% and 50% at one and five years respectively. High on-treatment platelet reactivity (HPR) in patients treated with aspirin and clopidogrel is associated with increased risk of recurrent cardiovascular events after percutaneous coronary interventions and coronary syndromes. Preliminary studies suggest that the prevalence of HPR in patients with critical limb ischemia treated with aspirin and clopidogrel is as high a 78.5%. In patients with coronary artery disease ticagrelor overcomes non-responsiveness to clopidogrel. However, the antiplatelet effect of ticagrelor in patients with critical limb ischemia is unknown.
Study Aim: This pilot study aims to investigate platelet function after switching from clopidogrel to ticagrelor in patients with critical limb ischemia.
Fifty patients with diagnosis of CLI (Rutherford class IV-VI) treated with clopidogrel 75 mg and aspirin 81 mg daily will be tested for inhibition of platelet aggregation using the VerifyNow P2Y12 and VASP assays before and 6±1 hours after their daily clopidogrel dose. All patients will then be switched from clopidogrel to ticagrelor 90 mg twice daily for two weeks and the VerifyNow and Vasodilator-Stimulated Phosphoprotein (VASP) platelet reactivity assays repeated, samples will be collected before and 6±1 hours after the last ticagrelor dose. For exploratory analysis, patients will be divided in two groups based on the P2Y12 reaction units (PRU): Group 1. High on treatment platelet reactivity on clopidogrel (HPR), defined as P2Y12 reaction units (PRU) ≥208 and Group 2. Appropriate platelet inhibition on clopidogrel (API), defined as P2Y12 reaction units (PRU) \<208. If subjects are withdrawn from the study prior to completion due to the high co-morbidity rate of this population, additional subjects will be enrolled to reach a total of 50 completed subjects for data analysis.
343 studies on the registry are indexed under Chronic Limb-Threatening Ischemia; 70 are open to participants now.
This study's enrollment of 53 is above the median of 45 across 233 interventional studies indexed under Chronic Limb-Threatening Ischemia.
Browse Chronic Limb-Threatening Ischemia studies →University of Southern California is the lead sponsor of 773 studies on the registry; 135 are open to participants now.
Of its 68 completed or terminated interventional studies of FDA-regulated products, 32 (47%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
All subjects will receive Ticagrelor.
Drug: Ticagrelor
All patients will be switched from clopidogrel to ticagrelor 90 mg twice daily for two weeks and the VerifyNow and VASP platelet reactivity assays repeated, samples will be collected before and 6±1 hours after the last ticagrelor dose.
Also known as: Brilinta
To Determine Platelet Inhibition Before and After Switching for Two Weeks From Clopidogrel to Ticagrelor in Patients With CLI.
Patients platelet inhibition was analyzed based on the P2Y12 reaction units (PRU) as high on treatment platelet reactivity (HPR), defined as P2Y12 reaction units (PRU) ≥208 and appropriate platelet inhibition on (API), defined as P2Y12 reaction units (PRU) \<208
Time frame: Two weeks
Establish the Number of Participants in the High On-treatment Platelet Reactivity (HPR) on Clopidogrel Group Who Demonstrated Appropriate Platelet Inhibition (API) After Switching to Ticagrelor for Two Weeks.
This measure was obtained by the number of participants who demonstrated high on treatment platelet reactivity (PRU \> / = 208) on Clopidogrel, and the number of participants who also resulted in the Appropriate Platelet Inhibition (PRU \< 208) after switching to Ticagrelor for two weeks of uninterrupted therapy x 100% .
Time frame: Two weeks
Establish the Number of Participants With Appropriate Platelet Inhibition on Clopidogrel Who Demonstrated Appropriate Platelet Inhibition After Switching to Ticagrelor for Two Weeks.
The measure was obtained from the number of participants in the Appropriate Platelet Inhibition (PRU \< 208) on Clopidogrel and who remained with Appropriate Platelet Inhibition after switching to Ticagrelor for two weeks of uninterrupted therapy x 100
Time frame: Two weeks
Evaluate the Correlation Between PRU and VASP-PRI in CLI Patients During Clopidogrel Versus Ticagrelor Antiplatelet Therapy.
Correlation between the P2Y12 Reaction Units (PRU) and the Vasodilator-Stimulated Phosphoprotein Assay-Platelet Reactivity Index (VASP-PRI) used to test the inhibition of platelet aggregation after two weeks of uninterrupted therapy with Clopidogrel versus Ticagrelor in CLI participants
Time frame: Two weeks
Patients with diagnosis of CLI (Rutherford class IV, V and VI) on continuous dual antiplatelet therapy with clopidogrel 75 mg and aspirin 81 mg daily for at least 14+2 days
| Milestone | Experimental |
|---|---|
| Started | 53 |
| Completed | 50 |
| Not completed | 3 |
| Withdrew: Adverse event | 3 |
Patients platelet inhibition was analyzed based on the P2Y12 reaction units (PRU) as high on treatment platelet reactivity (HPR), defined as P2Y12 reaction units (PRU) ≥208 and appropriate platelet inhibition on (API), defined as P2Y12 reaction units (PRU) \<208
| P2Y12 reaction units (PRU) | Ticagrelor |
|---|---|
| Clopidogrel Baseline | 173 (149 to 196) |
| Clopidogrel 6+-1 hour after the baseline dose | 140 (116 to 163) |
| Ticagrelor Baseline | 71 (47 to 94) |
| Ticagrelor 6+-1 hour after baseline | 63 (39 to 86) |
This measure was obtained by the number of participants who demonstrated high on treatment platelet reactivity (PRU \> / = 208) on Clopidogrel, and the number of participants who also resulted in the Appropriate Platelet Inhibition (PRU \< 208) after switching to Ticagrelor for two weeks of uninterrupted therapy x 100% .
| Participants | HPR on Clopidogrel and API on Ticagrelor |
|---|---|
| Establish the Number of Participants in the High On-treatment Platelet Reactivity (HPR) on Clopidogrel Group Who Demonstrated Appropriate Platelet Inhibition (API) After Switching to Ticagrelor for Two Weeks. | 17 |
The measure was obtained from the number of participants in the Appropriate Platelet Inhibition (PRU \< 208) on Clopidogrel and who remained with Appropriate Platelet Inhibition after switching to Ticagrelor for two weeks of uninterrupted therapy x 100
| Participants | API on Clopidogrel and API on Ticagrelor |
|---|---|
| Establish the Number of Participants With Appropriate Platelet Inhibition on Clopidogrel Who Demonstrated Appropriate Platelet Inhibition After Switching to Ticagrelor for Two Weeks. | 32 |
Correlation between the P2Y12 Reaction Units (PRU) and the Vasodilator-Stimulated Phosphoprotein Assay-Platelet Reactivity Index (VASP-PRI) used to test the inhibition of platelet aggregation after two weeks of uninterrupted therapy with Clopidogrel versus Ticagrelor in CLI participants
| Correlation Coefficient | Correlation of PRU and VASP-PRI |
|---|---|
| Clopidogrel | 0.73 |
| Ticagrelor | 0.47 |
| Overall Group | 0.6 |
Collected over Two weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Experimental | 0/53 (0%) | 1/53 (1.9%) | 1/53 (1.9%) |
| Event | Experimental |
|---|---|
| Hospitalization for PneumoniaRespiratory, thoracic and mediastinal disorders | 1/53 |
| Rheumatoid arthritis pericarditisImmune system disorders | 1/53 |
| Event | Experimental |
|---|---|
| Skin reactionSkin and subcutaneous tissue disorders | 1/53 |
The study analysis was based on the 50 patients who completed the study
| Age, Continuous(years) | Experimental |
|---|---|
| Mean | 65.3 ± 10.6 |
| Sex: Female, Male(Participants) | Experimental |
|---|---|
| Female | 23 |
| Male | 27 |
| Region of Enrollment(Participants) | Experimental |
|---|---|
| United States | 50 |
Plan to share: No
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Chronic Limb-Threatening Ischemia→
University of Southern California